A few of the most powerful villains present in the Justice League Superheroes comics include Starro, Brainiac, Lex Luthor, Amazo, Maxwell Lord, Prometheus, the Injustice Society and Crime Syndicate of America. Just like the heroes of the DC Universe, the villains are varied and full of unique character developments.
Starro proves to be the most powerful super villain who fights against the Justice League. He was the first to unite against the Superheroes. Brainiac uses his knowledge of technology to combat against the League. Lex Luthor is a powerful villain who is almost always behind every attack of the Justice League, especially those concerning Superman. Amazo is continuously being rebuilt in attempts to finally win against the League. Maxwell Lord is known for shooting the Blue Beetle. He was killed in the past, but has been brought back to life to continue in the war against the Heroes. Prometheus's greatest attribute is his ability to fight single-handed and hold off the League. He is also known for killing many and bringing rise to Arsenal.
The Injustice Society continues to accept new members to their group and is known for attacking the United States on numerous occasions. The Crime Syndicate of America proves to be a very deadly group. Each member is an exact opposite of the Justice League's heroes, with extremely strong powers and capabilities.